REVIEW ARTICLE – BREAST ONCOLOGY Intraoperative Radiation Therapy: A Critical Analysis of the ELIOT and TARGIT Trials. Part 1—ELIOT Melvin J. Silverstein, MD 1,2 , Gerd Fastner, MD 3 , Sergio Maluta, MD 4 , Roland Reitsamer, MD 5 , Donald A. Goer, PhD 6 , Frank Vicini, MD 7 , and David Wazer, MD 8,9 1 Breast Center, Hoag Memorial Hospital Presbyterian, Newport Beach, CA; 2 Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA; 3 Radiotherapy and Radio-Oncology Landeskrankenhaus, Paracelsus Medical University, Salzburg, Austria; 4 Radiation Oncology, Oncological Hyperthermia Unit—Medical Center, Verona, Italy; 5 Department of Senology, Paracelsus Medical University Salzburg, Salzburg, Austria; 6 Physics, IntraOp Medical, Sunnyvale, CA; 7 Radiation Oncology, St. Joseph Mercy Oakland, Pontiac, MI; 8 Radiation Oncology, Tufts University School of Medicine, Boston, MA; 9 Radiation Oncology, Albert Medical School of Brown University, Providence, RI ABSTRACT Introduction. Two randomized intraoperative radiation therapy trials for early-stage breast cancer were recently published. The ELIOT Trial used electrons (IOERT), and the TARGIT-A Trial Update used 50-kV X-rays (IORT). These studies were compared for similarities and differ- ences. The results were analyzed and used to determine which patients might be suitable for single-dose treatment. Method. The primary sources of data were the ELIOT Trial and TARGIT-A Trial, as well as a comprehensive analysis of the peer-reviewed literature of accelerated partial breast irradiation (APBI) using 50-kV X-rays or electrons. Studies published or presented prior to March 2014 were analyzed for efficacy, patient restrictions, complications, and outcome. Results. With a median follow-up of 5.8 years, the 5-year recurrence rates for ELIOT versus external beam radiation therapy (EBRT) patients were 4.4 % and 0.4 %, respec- tively, p = .0001. A low-risk ELIOT group was identified with a 5-year recurrence rate of 1.5 %. With a median follow-up of 29 months, the 5-year recurrence rates for the TARGIT-A versus EBRT patients were 3.3 % and 1.3 %, respectively, p = .042. Conclusion. With 5.8 years of median follow-up, IOERT appears to have a subset of low-risk women for whom IOERT is acceptable. With 29 months of median follow-up the results of IORT with 50-kV devices are promising, but longer follow-up data are required. At the current time, single-fraction IOERT or IORT patients should be treated under strict institutional protocols. When breast conserving surgery (BCS) is chosen, excision is commonly followed by 5 weeks of whole breast irradiation (WBI), with or without a boost to the tumor bed. Long radi- ation schedules are a burden for many women. 1,2 This has stimulated an interest in accelerated partial breast irradiation (APBI) that can reduce overall treatment time without com- promising oncological outcomes or cosmesis. 3,4 Intra- operative radiation therapy (IORT) is an attractive APBI approach because it delivers the entire radiation treatment during surgery. Two randomized IORT-APBI trials, ELIOT using electrons and TARGIT-A using 50-kV X-rays, have studied whether IORT can produce results that are equivalent to standard treatment. 5–7 In a series of 2 reports, we analyze these studies to determine whether IORT is ready for incor- poration into standard practice and to determine what patient cohorts might be suitable for single-dose treatment. METHODS The primary sources of data for these analyses were the ELIOT Trial and TARGIT-A Trials, as well as a compre- hensive review of peer-reviewed literature of APBI studies Ó The Author(s) 2014. This article is published with open access at Springerlink.com First Received: 23 June 2014; Published Online: 27 August 2014 M. J. Silverstein, MD e-mail: melsilver9@gmail.com Ann Surg Oncol (2014) 21:3787–3792 DOI 10.1245/s10434-014-3998-6